DPP 4 is the short name for an enzyme known as dipeptidyl peptidase 4. Dipeptidyl peptidase 4 breaks down two gut hormones known as incretins. Incretins are produced in the intestine when food is eaten, and they stimulate insulin secretion, which lowers blood glucose levels. In the disease known as type 2 diabetes, there is not enough insulin, or it is less effective, and blood glucose levels rise. Drugs to treat type 2 diabetes have been developed which inhibit DPP 4, preventing incretin breakdown and prolonging insulin secretion, increasing its effect.
The enzyme known as DPP 4 is found in a number of different sites in the human body, including the cells that line small arteries in the gut. It is sometimes referred to as dipeptidyl peptidase IV (DPP IV). Part of the structure of a protein known as CD26 is identical to dipeptidyl peptidase 4. CD26 is found in the membranes of many different cells, including T cells in the immune system, which it may help activate. The DPP 4 section of the molecule protrudes on the outside of the cell.
CD26 is also found in the nucleus of some cancer cells and is thought to play a role in the development and growth of certain tumors. In some cases the opposite occurs, and a reduction in CD26 and DPP 4 is associated with cancer progression. Dipeptidyl peptidase 4 is seen in reduced amounts in melanomas, where it may act as a tumor suppressor. Future research could give rise to cancer treatments which target CD26 and its enzyme DPP 4. In some cancers, blood levels of CD26 can give an indication of tumor behavior and prognosis which is more accurate than other cancer markers.
Inside the human gut, DPP 4 breaks down the incretins known as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulin-releasing polypeptide (GIP). Normally, both hormones stimulate insulin release, but the secretion of GLP-1 is greatly reduced in type 2 diabetes. As well as promoting insulin release, GLP-1 slows stomach emptying, lowers the appetite and, when necessary, prevents the hormone glucagon from raising blood sugar. These useful effects, together with an increase in insulin secretion, can be enhanced by drugs which inhibit DPP 4, and prevent GLP-1 from being broken down. Dipeptidyl peptidase 4-inhibitors have an advantage over many diabetes drugs in that they do not cause weight gain, and they are used as a second line of treatment after the principal diabetes drug, metformin.